the circadian clock protein timeless regulates phagocytosis of bacteria in drosophila生物钟蛋白的调节细菌在果蝇的吞噬作用.pdfVIP

The Circadian Clock Protein Timeless Regulates Phagocytosis of Bacteria in Drosophila 1. 2. 3¤a 3 3 Elizabeth F. Stone , Ben O. Fulton , Janelle S. Ayres , Linh N. Pham , Junaid Ziauddin , Mimi M. Shirasu-Hiza3¤b* 1 Department of Neurobiology and Behavior, Columbia University Medical School, New York, New York, United States of America, 2 Department of Genetics and Development, Columbia University Medical School, New York, New York, United States of America, 3 Department of Microbiology and Immunology, Stanford University Medical School, Stanford, California, United States of America Abstract Survival of bacterial infection is the result of complex host-pathogen interactions. An often-overlooked aspect of these interactions is the circadian state of the host. Previously, we demonstrated that Drosophila mutants lacking the circadian regulatory proteins Timeless (Tim) and Period (Per) are sensitive to infection by S. pneumoniae. Sensitivity to infection can be mediated either by changes in resistance (control of microbial load) or tolerance (endurance of the pathogenic effects of infection). Here we show that Tim regulates resistance against both S. pneumoniae and S. marcescens. We set out to characterize and identify the underlying mechanism of resistance that is circadian-regulated. Using S. pneumoniae, we found that resistance oscillates daily in adult wild-type flies and that these oscillations are absent in Tim mutants. Drosophila have at least three main resistance mechanisms to kill high levels of bacteria in their hemolymph: melanization, antimicrobial peptides, and phagocytosis. We found that melanization is not circadian-regulated. We further found that basal levels of